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BBB and epilepsy

Song Hee Lee, Bo Young Choi, Jin Hee Kim, A Ra Kho, Min Sohn, Hong Ki Song, Hui Chul Choi, Sang Won Suh
Choline alfoscerate (α-GPC) is a common choline compound and acetylcholine precursor in the brain, which has been shown to be effective in the treatment of Alzheimer's disease and dementia. α-GPC has been shown to enhance memory and cognitive function in stroke and Alzheimer's patients but currently remains untested in patients suffering from epilepsy. This study aimed to evaluate whether α-GPC treatment after seizure can ameliorate seizure-induced cognitive impairment and neuronal injury. The potential therapeutic effects of α-GPC on seizure-induced cognitive impairment were tested in an animal model of pilocarpine-induced seizure...
October 17, 2016: Brain Research
Barbara Ruozi, Daniela Belletti, Francesca Pederzoli, Flavio Forni, Maria Angela Vandelli, Giovanni Tosi
The research of efficacious non-invasive therapies for the treatment of brain diseases represents a huge challenge, as people affected by disorders of the Central Nervous System (CNS) will significantly increase. Moreover, Blood-Brain Barrier (BBB) is a key factor in hampering a number of effective drugs to reach the CNS. This review is therefore focusing on possible interventions of nanomedicine-based approaches in selected diseases affecting the CNS. A wide overview of the most outstanding results on preclinical evaluations of the potential of nanomedicine in brain diseases (i...
September 15, 2016: CNS & Neurological Disorders Drug Targets
Elena Gatta, Aroldo Cupello, Mario Di Braccio, Giancarlo Grossi, Mauro Robello, Francesca Scicchitano, Emilio Russo, Giovambattista De Sarro
Herein, we tested in a model of generalized reflex epilepsy in mice different 1,4-benzodiazepines and 1,5-benzodiazepines with agonistic activity at the GABAA receptor population contributing to the peak component of the chloride current elicited by GABA in cerebellar granule cells (CGCs) in culture. The substances have all higher lipophilia than clobazam, an antiepileptic drug well known and used in human therapy. This ensures that they all can pass relatively easily the blood-brain barrier (BBB). The benzodiazepines were administered intraperitoneally (i...
September 15, 2016: Journal of Molecular Neuroscience: MN
Su-Ji Min, Tae-Cheon Kang
Brain-blood barrier (BBB) disruption results in vasogenic edema, which is involved in the pathogenesis of epilepsy. Following status epilepticus (SE), up-regulated transient receptor potential canonical channel-3 (TRPC3), a Ca(2+)-permeable cation channels in endothelial cells, is relevant to vasogenic edema formation in the rat piriform cortex. In addition, pyrazole-3 (Pyr-3, a TRPC3 inhibitor) attenuated SE-induced vasogenic edema. However, the upstream regulators of TRPC3 expression in vasogenic edema formation have been unclear...
September 10, 2016: Neuroscience
Nicholas H Varvel, Jonas J Neher, Andrea Bosch, Wenyi Wang, Richard M Ransohoff, Richard J Miller, Raymond Dingledine
The generalized seizures of status epilepticus (SE) trigger a series of molecular and cellular events that produce cognitive deficits and can culminate in the development of epilepsy. Known early events include opening of the blood-brain barrier (BBB) and astrocytosis accompanied by activation of brain microglia. Whereas circulating monocytes do not infiltrate the healthy CNS, monocytes can enter the brain in response to injury and contribute to the immune response. We examined the cellular components of innate immune inflammation in the days following SE by discriminating microglia vs...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
Maria Feldmann, Matthias Koepp
Resistance to antiepileptic drugs (AED) remains a major problem in clinical epileptology. This pharmacoresistance is independent of the choice of AEDs. Different hypotheses have been proposed to explain the neurobiological basis for pharmacoresistance in epilepsy. The transporter hypothesis is the mostly investigated theory. Hereby, overexpression of multidrug efflux transporters such as P-glycoprotein (Pgp) at the blood-brain-barrier (BBB) is thought to be involved in pharmacoresistance in epilepsy by extruding AEDs from their target site...
August 10, 2016: Current Pharmaceutical Design
Natalia Brzozowska, Kong M Li, Xiao Suo Wang, Jessica Booth, Jordyn Stuart, Iain S McGregor, Jonathon C Arnold
Cannabidiol (CBD) is currently being investigated as a novel therapeutic for the treatment of CNS disorders like schizophrenia and epilepsy. ABC transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) mediate pharmacoresistance in these disorders. P-gp and Bcrp are expressed at the blood brain barrier (BBB) and reduce the brain uptake of substrate drugs including various antipsychotics and anticonvulsants. It is therefore important to assess whether CBD is prone to treatment resistance mediated by P-gp and Bcrp...
2016: PeerJ
Jonathan Vinet, Ilia D Vainchtein, Carlotta Spano, Carmela Giordano, Domenico Bordini, Giulia Curia, Massimo Dominici, Hendrikus W G M Boddeke, Bart J L Eggen, Giuseppe Biagini
Activated microglia, astrogliosis, expression of pro-inflammatory cytokines, blood brain barrier (BBB) leakage and peripheral immune cell infiltration are features of mesial temporal lobe epilepsy. Numerous studies correlated the expression of pro-inflammatory cytokines with the activated morphology of microglia, attributing them a pro-epileptogenic role. However, microglia and myeloid cells such as macrophages have always been difficult to distinguish due to an overlap in expressed cell surface molecules. Thus, the detrimental role in epilepsy that is attributed to microglia might be shared with myeloid infiltrates...
August 2016: Glia
Sreekanth Puttachary, Shaunik Sharma, Saurabh Verma, Yang Yang, Marson Putra, Achala Thippeswamy, Diou Luo, Thimmasettappa Thippeswamy
Status epilepticus (SE) initiates epileptogenesis to transform normal brain to epileptic state which is characterized by spontaneous recurrent seizures (SRS). Prior to SRS, progressive changes occur in the brain soon after SE, for example, loss of blood-brain barrier (BBB) integrity, neuronal hyper-excitability (epileptiform spiking), neuroinflammation [reactive gliosis, high levels of reactive oxygen/nitrogen species (ROS/RNS)], neurodegeneration and synaptic re-organization. Our hypothesis was that modification of early epileptogenic events will alter the course of disease development and its progression...
September 2016: Neurobiology of Disease
Francesco M Noé, Elisa Bellistri, Francesca Colciaghi, Barbara Cipelletti, Giorgio Battaglia, Marco de Curtis, Laura Librizzi
OBJECTIVE: Systemic administration of kainic acid (KA) is a widely used procedure utilized to develop a model of temporal lobe epilepsy (TLE). Despite its ability to induce status epilepticus (SE) in vivo, KA applied to in vitro preparations induces only interictal-like activity and/or isolated ictal discharges. The possibility that extravasation of the serum protein albumin from the vascular compartment enhances KA-induced brain excitability is investigated here. METHODS: Epileptiform activity was induced by arterial perfusion of 6 μm KA in the in vitro isolated guinea pig brain preparation...
June 2016: Epilepsia
Ziyan Fang, Shuda Chen, Jiaming Qin, Bao Chen, Guanzhong Ni, Ziyi Chen, Jueqian Zhou, Ze Li, Yuping Ning, Chuanbin Wu, Liemin Zhou
P-glycoprotein (Pgp) overexpression in the blood brain barrier (BBB) is hypothesized to lower brain drug concentrations and thus inhibit anticonvulsant effects in drug-resistant epilepsy. Recently, the poly(butylcyanoacrylate) (PBCA) nanoparticle system was shown to overcome the obstacle of the BBB to deliver drugs into the brain. To determine whether pluronic P85-coated phenytoin poly(butylcyanoacrylate) nanoparticles (P85-PHT-PBCA-NPs) target PHT to the brain, PHT-resistant rats overexpressing Pgp in the BBB were screened by response to PHT treatment after chronic temporal lobe epilepsy induced by lithium-pilocarpine, followed by direct verification of PHT transport via measurement of brain PHT concentrations using microdialysis...
August 2016: Biomaterials
Yi Guo, Li Jiang
OBJECTIVES: Abnormal drug transporter expression or function in the brain may lead to decreased concentrations of antiepileptic drugs (AEDs) in the central nervous system in patients with drug-resistant epilepsy. We previously showed the influx transporter organic anion transport polypeptide 2 (Oatp2) was expressed in rat brain microvascular endothelial cells (BMECs). Seizures decrease expression of Oatp2, but it remains unclear whether Oatp2 transports AEDs. In this study, we utilized rat BMECs as an in vitro model of the blood-brain barrier (BBB) to study Oatp2-mediated transport of valproic acid (VPA), the most common clinically used AEDs...
July 2016: Neurological Research
Andreas M Grabrucker, Barbara Ruozi, Daniela Belletti, Francesca Pederzoli, Flavio Forni, Maria Angela Vandelli, Giovanni Tosi
While the role of the blood-brain barrier (BBB) is increasingly recognized in the (development of treatments targeting neurodegenerative disorders, to date, few strategies exist that enable drug delivery of non-BBB crossing molecules directly to their site of action, the brain. However, the recent advent of Nanomedicines may provide a potent tool to implement CNS targeted delivery of active compounds. Approaches for BBB crossing are deeply investigated in relation to the pathology: among the main important diseases of the CNS, this review focuses on the application of nanomedicines to neurodegenerative disorders (Alzheimer, Parkinson and Huntington's Disease) and to other brain pathologies as epilepsy, infectious diseases, multiple sclerosis, lysosomal storage disorders, strokes...
January 2016: Tissue Barriers
Steven M LeVine
Leakage of the blood-brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species...
2016: BMC Neurology
Avijit Dey, Xu Kang, Jiange Qiu, Yifeng Du, Jianxiong Jiang
As a crucial component of brain innate immunity, neuroinflammation initially contributes to neuronal tissue repair and maintenance. However, chronic inflammatory processes within the brain and associated blood-brain barrier (BBB) impairment often cause neurotoxicity and hyperexcitability. Mounting evidence points to a mutual facilitation between inflammation and epilepsy, suggesting that blocking the undesired inflammatory signaling within the brain might provide novel strategies to treat seizures and epilepsy...
June 2016: Trends in Pharmacological Sciences
Ekta Khambhla, Viral Shah, Kalpesh Baviskar
The current epoch has witnessed a lifestyle impregnated with stress, which is a major cause of several neurological disorders. High morbidity and mortality rate due to neurological diseases and disorders have generated a huge social impact. Despite voluminous research, patients suffering from fatal and/or debilitating CNS diseases such as brain tumors, HIV, encephalopathy, Alzheimer's, epilepsy, Parkinson's, migraine and multiple sclerosis outnumbered those suffering from systemic cancer or heart diseases. The brain being a highly sensitive neuronal organ, has evolved with vasculature barriers, which regulates the efflux and influx of substances to CNS...
2016: Current Pharmaceutical Design
Anne Mahringer, Gert Fricker
INTRODUCTION: The blood-brain barrier (BBB) possesses an outstanding ability to protect the brain against xenobiotics and potentially poisonous metabolites. Owing to this, ATP binding cassette (ABC) export proteins have garnered significant interest in the research community. These transport proteins are predominantly localized to the luminal membrane of brain microvessels, where they recognize a wide range of different substrates and transport them back into the blood circulation. AREAS COVERED: This review summarizes recent findings on these transport proteins, including their expression in the endothelial cell membrane and their substrate recognition...
May 2016: Expert Opinion on Drug Metabolism & Toxicology
Tingting Fu, Qingxia Kong, Huaqiang Sheng, Lingyun Gao
Purpose. Although active targeting of drugs using a magnetic-targeted drug delivery system (MTDS) with superparamagnetic iron oxide nanoparticles (SPIONs) is a very effective treatment approach for tumors and other illnesses, successful results of drug-resistant temporal lobe epilepsy (TLE) are unprecedented. A hallmark in the neuropathology of TLE is brain inflammation, in particular the activation of interleukin-1β (IL-1β) induced by activated glial cells, which has been considered a new mechanistic target for treatment...
2016: Neural Plasticity
Yonatan Serlin, Tali Shafat, Jaime Levy, Aaron Winter, Marina Shneck, Boris Knyazer, Yisrael Parmet, Hadar Shalev, Ehud Ur, Alon Friedman
INTRODUCTION: Diabetic retinopathy (DR) is a common vasculopathy categorized as either non-proliferative (NPDR) or proliferative (PDR),characterized by dysfunctional blood-retinal barrier (BRB) and diagnosed using fluorescein angiography (FA). Since the BRB is similar in structure and function to the blood-brain barrier (BBB) and BBB dysfunction plays a key role in the pathogenesis of brain disorders, we hypothesized that PDR, the severe form of DR, is likely to mirror BBB damage and to predict a worse neuropsychiatric outcome...
May 2016: Psychoneuroendocrinology
Maysam Z Pedram, Amir Shamloo, Aria Alasty, Ebrahim Ghafar-Zadeh
One of the most common neurological brain disorder is epilepsy that happen as an abrupt seizure. Around 30% of patients with epilepsy resist to all forms of medical treatments and, therefore, the removal of epileptic brain tissue is the only solution to get these patients free from chronical seizures. Discovering the epileptic region is a first key into the treatment. In this paper, we introduced a method for epilepsy detection. In this method superparamagnetic nanoparticle, (SPMN) is used as a sensing material in order to investigate the epileptic area...
August 2015: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
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